TABLE 2

Inhibition of uptake transporters by fluorescent bile acid derivatives

Transport experiments were performed as described in Material and Methods. The following substrates were used: NTCP, OATP1B3: 5 µM taurocholate; ASBT: 1 µM taurocholate; and OATP1B1 and OATP2B1: 1 µM estrone-3-sulfate. Transport was measured for 40 seconds. Substrate uptake values in % were corrected for uptake into WT CHO cells. Uptake in the absence of inhibitor was set to 100%. Results are the mean from two to four independent experiments with three technical replicates.

Compound[I]NTCPOATP1B1OATP1B3OATP2B1ASBT
µM
CenNBD0100100100100100
0.198.510110890.995.8
1108.395.183.076.686.5
1038.764.926.623.076.4
1004.99.422.93.664.2
CenDNS0100100100100100
0.185.998.882.794.085.5
149.189.257.055.580.1
107.830.413.011.559.4
1002.416.541.77.447.9
CenPB0100100100100100
0.193.898.769.095.447.7
173.993.762.089.840.4
1028.972.728.655.050.4
1005.851.219.015.751.0
CDCenNBD0100100100100100
0.185.699.713286.399.1
167.595.695.585.4108
1015.790.834.164.7113
10017.786.841.266.991.7
CDCenDNS0100100100100100
0.192.999.883.087.868.9
161.894.364.087.9123
1046.683.355.973.0164
10046.284.050.562.7109
CDCenPB0100100100100100
0.164.591.956.798.043.4
129.671.537.560.542.3
106.736.328.813.248.6
1003.93.119.83.745.3
AcenNBD0100100100100100
0.175.893.287.583.079.0
187.689.410386.798.8
1011886.310383.7100
10075.878.388.449.1144
AcenDNS0100100100100100
0.192.799.610995.882.0
111094.810295.792.2
1012093.594.811499.6
10080.290.869.9147101
AcenPB0ND100100100ND
0.1ND99.781.399.2ND
1ND96.863.896.4ND
10ND96.162.594.3ND
100ND89.062.568.8ND
  • ND, not determined.